In humans, mammals, and perhaps all vertebrates, sphingolipids exist as a family of cellular signaling molecules and have been shown to be involved in a wide range of biological processes ranging from proliferation to apoptosis. As such, sphingolipid signaling has garnered the attention of numerous researchers as an attractive candidate for pharmacological manipulation. The synthetic pathway of one prominent sphingolipid, sphingosine 1-phosphate (S1P), has been implicated in a variety of disease states such as cancer, sickle cell disease, multiple sclerosis, and renal fibrosis. Formation of S1P is facilitated from the ATP dependent phosphorylation of sphingosine (Sph) through its generative enzyme's sphingosine kinase 1 and 2 (SphK1 and SphK2). Inhibition of SphK1 and SphK2 results in the manipulation of S1P levels, which has been shown to be therapeutic in various animal models of disease. While there are multiple examples of potent SphK1-selective and dual SphK1/2 inhibitors, SphK2-selective inhibitors are scarce. Herein, we describe the design, synthesis and biological testing of SphK2-selective inhibitors. We first describe the discovery that introducing a trifluoromethyl group onto the internal aryl ring of our inhibitor scaffold led to superior selectivity and potency towards SphK2. We demonstrate that the trifluoromethyl moiety is interacting with a previously unknown side cavity in the substrate binding site of SphK2 that is unique and could be exploited in the design of SphK2-selective inhibitors. The synthesis of 21 derivatives with various substituents spanning off the internal aryl ring was completed, therefore characterizing the preferred size and chemical nature of moieties positioned in that portion of the binding site. This work led to the development of the most potent SphK2-selective inhibitor known at the time. We then describe the transformation of our SphK2-selective inhibitors into an orally bioavailable drug. We explain how the guanidine functionality on our inhibitor scaffold hinders our compounds from being orally bioavailable. Consequently, a library of 24 derivatives with various modifications to the guanidine functionality was synthesized and evaluated for improved orally bioavailability. Highlighted in this work is the development of the most potent SphK2-selective inhibitor currently known 3.14 (SLS1081832), which displays a hSphK2 Ki of 82 nM and 122-fold selectivity for SphK2. Chemical modification and in vivo assessment of 3.14 (SLS1081832) prodrugs was explored. / Doctor of Philosophy / In humans, sphingosine 1-phosphate (S1P) is a signaling molecule that is generated through an ATP dependent reaction of sphingosine (Sph) via sphingosine kinase 1 and 2 (SphK1 and SphK2). Furthermore, S1P has been shown to be implicated in various diseases such as cancer, sickle cell disease, multiple sclerosis, and renal fibrosis. Inhibition of SphK1 and SphK2 has been shown to be therapeutic towards the symptoms of these diseases. Therefore, in order to alleviate these disorders, the concentrations of S1P must be controlled through pharmacological inhibition of SphK1 and SphK2. There are multiple reported examples of potent SphK1-selective and dual SphK1/2 inhibitors; however, SphK2-selective inhibitors are scarce. This work describes the synthesis and biological assessment of 21 compounds for their effectiveness in selectively targeting and inhibiting SphK2. The work led to the discovery of a previously unrecognized side cavity in the binding pocket of SphK2 that enhances inhibitor potency and selectivity towards SphK2. Furthermore, studies characterizing the preferred size and chemical nature of moieties positioned in that portion of the binding site led to the development of the most potent SphK2- selective inhibitor known at the time. Building on this work, we next focused on the transformation of our SphK2-selective inhibitors into a drug that could be administered orally. We describe the synthesis of 24 compounds with various modifications to one portion of our scaffold and their effect on improved orally bioavailability. This work led to the development of the most potent SphK2-selective inhibitor currently known 3.14 (SLS1081832).

Malaria, a disease caused by the parasite Plasmodium, continues to be one of the deadliest diseases worldwide. The WHO reported over 627,000 deaths in 2020, and over 1 billion people are at risk of infection. Even though Artemisinin-based Combination Therapies (ACT) are the current standard of care for malaria, the emergence of drug resistance generates a constant need to develop and synthesize new drugs. Tetrahydro-β-carboline acid (THβC) 1-(2,4-dichlorophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-2-ium-3-carboxylate (MMV008138) has promising antimalarial properties; it was discovered by screening the Malaria Box with the so-called IPP Rescue assay. This assay identified MMV008138 as an inhibitor of the MEP pathway, which produces essential isoprenoid precursors (IPP and DMAPP) in the malaria parasite P. falciparum (EC50 250 ± 70 nM, IPP rescue 100% @ 2.5 μM). Subsequent investigation revealed that (1R,3S)-configuration and 2',4'-dihalogen substitution were critical for the activity of this compound, and that substitution of the non-aromatic ring was not tolerated. To search for new antimalarial structures, our collaborator Dr. Max Totrov constructed a generalized 3D pharmacophore-based on MMV008138 and 92 of its analogs and used it for a virtual ligand screen (VLS) of the 13K compound hit set from which MMV008138 had been selected. This exercise identified TCMDC-140230, a THβC, 1-(3,4-dichlorophenyl)-8-methyl-N-(2-(methylamino)ethyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxamide (undefined stereochemistry) reported having nearly the same potency of MMV008138. Synthesis of the stereoisomers of compound TCMDC-140230 was accomplished via Pictet-Spengler reaction of (S)- and (R)-7-methyl tryptophan methyl ester and 3,4-dichlorobenzaldehyde. The individual stereoisomeric esters were converted to the corresponding amides, but none of the stereoisomers of TCMDC-140230 were potent antimalarials (IC50 = 1,300 – 3,700 nM). However, a significant amount of oxidized byproduct 1-(3,4-dichlorophenyl)-8-methyl-N-(2-(methylamino)ethyl)-9H-pyrido[3,4-b]indole-3-carboxamide (MMV1803522) was observed in the synthesis of (1S,3S)- and (1R,3R)-TCDMC-140230. This achiral β-carboline amide (PRC1584, IC50 = 108 ± 7 nM) proved more potent towards P. falciparum than MMV008138 and its toxicity was not reversed by co-application of IPP. Thus, the antimalarial target of MMV1803522 is distinct from that of MMV008138. Most importantly, MMV1803522 at 40 mg/kg/day (oral) cured P. berghei malaria infection in mice. The lead compound also was found to have a good safety profile. Medicines for Malaria Venture (MMV) has expressed interest in this compound which is now also known as MMV1803522. The results from these biological assays gave the insight to develop new analogs that have better asexual blood stage inhibition potency. Extensive structure-activity relationship studies were conducted by synthesizing analogs of the compound MMV1803522. The studies were mainly focused on analyzing the effect of aliphatic substitutions, how well the potency can be improved with different D-ring substitutions, and amide substitutions. In addition to this structural optimization, several metabolism studies were also conducted on this new lead compound. The potency study results of C1 alkyl-substituted analogs of MMV1803522 showed that aromatic substitutions are required at C1 for maintaining good inhibition potency. The heteroaryl substituents at C1 were found to be slightly less potent than the lead compound MMV1803522. Synthesis of analogs without C8 methyl group as in lead compound showed an EC50 < 100 nM is possible with a C8 hydrogen substitution. Most noteworthy is 3,4,5-trichlotophenyl-bearing compound 3.20a, which had an EC50 of 54 ± 8 nM. This compound is twice as potent as MMV1803522. Equipotent analogs to MMV1803522 were also synthesized with different amide substituents. The metabolism studies showed low solubility for compounds having an EC50 less than or close to 100 nM. Unfortunately, the intrinsic clearance rate of several selected compounds was found to be higher than MMV1803522. These results left us with scope for the development of new analog compounds. The emerging structure-activity relationship within this scaffold and outline of remaining challenges to improve potency sub-100 nM without compromising moderate solubility and good metabolic stability are in progress. / Doctor of Philosophy / Malaria is a global health problem that causes significant sickness and death annually in the developing world. The emergence of resistant parasite strains of malaria massively challenges efforts to eliminate this threat. To control the spread of malaria, there is a continuous need for the development of new antimalarial drugs that ideally offer a single-dose cure and new mechanism of action. One such promising target, called, Methyl Erythrytol Phosphate (MEP) pathway which produces IPP and DMAPP, are important isoprenoid precursors required in living beings. A compound MMV008138 was identified from a collection of compounds that exhibited antimalarial activity, the so-called "Malaria Box", and this compound was further analyzed for several biological assays. Unfortunately, MMV008138 was unsuccessful Since it was found toxic in mice when ingested orally. The efforts to develop structurally similar analogs of MMV008138 resulted in the accidental discovery of a compound that inhibits the parasites' growth much better than the former compound. This compound has a similar molecular structure to MMV008138, and the Medicines for Malaria organization (MMV) has designated it as MMV1803522. The newly obtained compound and its analogs were investigated and found to have promising potency to inhibit the growth of the malarial parasite Plasmodium falciparum. Multiple biological assays were conducted and found that even though MMV1803522 is toxic to malarial parasites, it does not show toxicity to other cells. The studies in mice showed that it was not toxic orally. Also, it was found to be non-toxic towards several mammalian cell lines. The development of structurally similar analogs can help in improving the potency of the compound, make a better orally bioavailable compound, and improve oral efficacy. Analyzing these results will help to determine the mechanism of action of the compound.

It has long been known that ship wakes are observable by synthetic aperture radar. However, incomplete physical understanding has prevented the development of simulation tools that can predict both the structure and persistence of wakes in the ocean environment. It is the focus of this work to develop an end-to-end multi-scale modeling-and-simulation methodology that captures the known physics between the source of disturbance and the sensor. This includes turbulent hydrodynamics, free-surface effects, environmental forcing through Langmuir-type circulations, generation of surface currents and redistribution of surface-active substances, surface-roughness modification, and simulation of the signature generated by reflection and scattering of electromagnetic waves from the ocean surface. The end-to-end methodology is based upon several customized computational fluid dynamics solvers and empirical models which are linked together. The unsteady Reynolds-averaged Navier-Stokes equations, including models for the Craik-Leibovich vortex force and near surface Reynolds-stress anisotropy, are solved at full-scale Reynolds and Froude numbers on domains that extend tens of kilometers behind the ship. A parametric study is undertaken to explore the effects of ship heading, ship propulsion, ocean-wave amplitude and wavelength, and the relative importance of Langmuir-type circulations vs. near-surface Reynolds-stress anisotropy on the generation of surface currents that are transverse to the wake centerline. Due to the vortex force, the structure of the persistent wake is shown to be a function of the relative angle between the ambient long-wavelength swell and the ship heading. Ships operating in head seas observe 1-3 streaks, while ships operating in following seas observe 2 symmetric streaks. Ships operating in calm seas generate similar wakes to those in following seas, but with reduced wake width and persistence. In addition to the structure of the persistent wake, the far wake is shown to be dominated by ship-induced turbulence and surface-current gradients generating a wide center wake. The redistribution of surface-active substances by surface currents is simulated using a scalar-transport model on the ocean surface. Simulation of surface-roughness modification is accomplished by solving a wave-action balance model which accounts for the relative change in the ambient wave-spectrum by the surface currents and the damping-effects of surface-active substances and turbulence. Simulated returns from synthetic aperture radar are generated with two methods implemented. The first method generates a perfect SAR image where the instrument and platform based errors are neglected, but the impact of a randomized ocean field on the radar cross section is considered. The second method simulates the full SAR process including signal detection and processing. Comparisons are made to full-scale field experiments with good agreement between the structure of the persistent wake and observed SAR imagery. / 1 / It has long been known that ship wakes are observable by synthetic aperture radar. However, incomplete physical understanding has prevented the development of simulation tools that can predict both the structure and persistence of wakes in the ocean environment, which is critical to understanding both the design and operation of maritime remote sensors as well as providing tactically relevant operational guidance and awareness of the maritime domain. It is the focus of this work to develop an end-to-end multi-scale modeling-and simulation methodology that captures the known physics between the source of disturbance and the sensor. This includes turbulent hydrodynamics, free-surface effects, environmental forcing, generation of surface currents and redistribution of surface-active substances, surface-roughness modification, and simulation of the signature from the ocean surface. The end-to-end methodology is based upon several customized computational fluid dynamics solvers and empirical models. The unsteady Reynolds-averaged Navier-Stokes equations, including models to account for environmental effects and near-surface turbulence, are solved at full-scale on domains that extend tens of kilometers behind the ship. A parametric study is undertaken to explore the effects of ship heading, ship propulsion, ocean-wave amplitude and wavelength, and the relative importance of environmental forcing vs. near-surface turbulence on the generation of surface currents that are transverse to the wake centerline. Due to the environmental forcing, the structure of the persistent wake is shown to be a function of the relative angle between the ambient long-wavelength swell and the ship heading. Ships operating in head seas observe 1-3 streaks, while ships operating in following seas observe 2 symmetric streaks. Ships operating in calm seas generate similar wakes to those in following seas, but with reduced wake width and persistence. In addition to the structure of the persistent wake, the far wake is shown to be dominated by ship-induced turbulence and surface-current gradients generating a wide center wake. The redistribution of surface films by surface currents is simulated using a scalar-transport model on the ocean surface. Simulation of surface-roughness modification is accomplished by solving a wave-action-balance model which accounts for the relative change in the ambient surface profile by the surface currents and the damping-effects of surface-active substances and turbulence. Simulated returns from synthetic aperture radar are generated with two methods implemented. The first method generates a perfect SAR image where the instrument and platform based errors are neglected, but the impact of a randomized ocean field on the radar cross section is considered. The second method simulates the full SAR process including signal detection and processing. Comparisons are made to full-scale field experiments with good agreement between the structure of the persistent wake and observed SAR imagery.

No / A procedure to reduce the effect of the mobile antenna on the handset by using balanced antennas has been investigated. Use of this type of antenna may degrade the antenna performance, such as bandwidth and gain, although it can cause less effect on the body to which they are adjacent. If the antennas are well designed, the maximum specific absorption rate (SAR) values are likely to be reduced when placed next to the head, since the coupling of such antennas to the body of the handset is very weak. A study on balanced and unbalanced antennas for mobile handsets next to the human head is presented, using a hybrid electromagnetics method for the analysis. The method uses the hybridisation technique between the frequency-domain method of moments (MoM) and the finite-difference time-domain method (FDTD). The antenna was modelled using MoM whereas the head tissues were modelled using FDTD. Two antennas were designed and investigated with respect to the SAR and radiation performance for two different antenna positions on the top edge of a mobile handset. Radiation patterns are presented and compared, with and without the head, and the maximum SAR values and field distributions inside the head are discussed. The balanced antenna shows good improvements with respect to the unbalanced antenna in terms of the SAR values and variations of the input impedances.

This thesis investigates the European Union’s response to the refugee crisis in the Mediterranean Sea, focusing on the strategy of externalizing border controls through agreements with Turkey and Libya. Employing a combination of qualitative textual analysis and interviews, the study examines the humanitarian and legal implications of these agreements, particularly in relation to the criminalization of NGOs’ activities on the Central Mediterranean Route. The findings reveal a dual process of criminalization, both at the European level through operational shifts and the implementation of Codes of Conduct, and at the national level through policies targeting NGOs, such as Italy’s “Codice di Condotta per le ONG” and “decreto Salvini-bis”. The examples of the SeaWatch-3 and IUVENTA boats demonstrate how these processes hinder NGOs’ operations and shape public discourse on migration. The thesis concludes by highlighting the ongoing challenges in the Mediterranean Sea and the need for further research to understand their implications fully.

Diese Arbeit ist ein empirischer Versuch zu verstehen, warum und wie Energieunternehmen Nachhaltigkeit durch Sustainability Accounting and Reporting institutionalisieren und wie sie von zahlreichen institutionellen Mechanismen im Rahmen der Institutionentheorie und der Stakeholder sowie aus deren Ansprüchen im Rahmen der Stakeholder Theorie beeinflusst werden, Theorien, die sich gegenseitig bedingen. Diese Arbeit möchte sich anhand normativer und deskriptiver Literatur über die Praktikabilität des Konzeptes und der Systeme informieren und durch die Entwicklung einer Fallstudie ein praktisches Beispiel vorstellen. Ziel dieser Arbeit ist die Entwicklung eines unternehmerischen Nachhaltigkeitssystems des Fallbeispielunternehmens, das pragmatisch zielgetrieben und – basierend auf den strategischen Schwerpunkten des Managements – auf die Einflüsse und Ansprüche der Stakeholder abgestimmt ist. Dafür wird die Fallstudie das Konzept des Sustainability Accounting and Re-porting anhand des regionalen Energieversorgungsunternehmens ReVU untersuchen und die Institutionalisierung prüfen. Im Rahmen der Stakeholderanalyse werden auch die Branche und der Wettbewerb auf ihre Nachhaltigkeit untersucht. Somit ist zu überprüfen, ob auch für ReVU Nachhaltigkeit ein Thema ist, in welcher Form und Ausprägung es zu implementieren wäre und welchen Nutzen es überhaupt bringen könnte. Im Ergebnis ist zu sehen, dass verschiedene institutionelle Mechanismen und das Stakeholdermanagement auf das nachhaltige Handeln des Unternehmens einwirken. Besonders ist im Moment der normative Druck der gesellschaftlichen Erwartungen aufgrund aktueller Ereignisse zu spüren, der auf die regulative Gesetzgebung der Energie- und Klimapolitik wirkt und die Energiewende beschleunigt. Diese nachhaltige Entwicklung ist auch kulturell-kognitiv in der Branche und bei den Wettbewerbern zu sehen. Dadurch ist ein deutlicher Wettbewerbsdruck zu bemerken, der auf dem Zusammenspiel von normativen, regulativen und kulturell-kognitiven Mechanismen beruht und durch das mimetische Verhalten zu einem Isomorphismus von nachhaltigen Strategien und Maßnahmen sowie Managementsystemen mit dem besonderen Bezug zur Ökologie führt.

Recent development in electronics for mobile devices has led to the decrease in sizes and cost of autonomous complex embedded systems such as satellites. It is now possible to build a satellite quicker and only for a fraction of previous costs by using Commercial Off The Shelf (COTS) components. Yet, there are some obstacles that need to be overcome before a successful small satellite can be designed. Among these are the radiation environment, thermal issues, the overall system complexity and tight schedules. This thesis addresses these issues and proposes an overall approach for designing small satellites’ electronics. This approach can be summarised in 6 recommendations: Keep it simple Use fast hardware iterations Do not use space grade components Use a single string design on the system level (no redundancy) Design with limited trust in the software Use simple, accessible and easy updatable documentation With respect to those recommendations an on board data processing system, the Processing Board, has been designed for the ICEYE-1 satellite. The ICEYE-1 satellite is a fully commercial Synthetic Aperture Radar (SAR) satellite that will be launched in December 2017. The designed board has been manufactured and verified during airborne test campaigns. / Nya elektronikutvecklingar för mobiltelefoner har lett till en minskning av storlek och kostnader för andra autonoma komplexa inbyggda system som t.ex. satelliter. Så kallade småsatelliter kan numera byggas snabbare och för endast en bråkdel av tidigare kostnader med hjälp av Commercial Off The Shelf (COTS) komponenter. Det finns dock vissa hinder som måste övervinnas om man vill designa en pålitligt fungerande småsatellit. Till dessa kan räknas strålningsmiljön, väl fungerande värmeledning, det totala systemets komplexitet samt snäva tidtabeller. Detta examensarbete behandlar dessa frågor och föreslår en övergripande strategi för att designa elektronik för småsatelliter. Detta tillvägagångssätt kan sammanfattas i 6 rekommendationer: Håll det enkelt Implementera snabba hårdvaruiterationer Använd inte rymdklassade komponenter Använd ingen redundans på systemnivå Designa med en begränsad tilltro på mjukvaran Dokumentera på ett enkelt, tillgängligt och lätt uppdateringsbart sätt Dessa rekommendationer har använts till att utveckla ett databehandlingssystem, kallat "Processing Board", till småsatelliten ICEYE-1. ICEYE-1 är en kommersiell Synthetic Aperture Radar (SAR) satellit som kommer att skjutas i omloppsbana i december 2017. Databehandlingssystemet i fråga har utvecklats och verifierats i samband med flygplansburna testkampanjer.

<p>U&nbsp; radu&nbsp; su&nbsp; ostvarene&nbsp; vi&scaron;efazne&nbsp; sinteze&nbsp; većeg&nbsp; broja&nbsp; analoga&nbsp; prirodnih&nbsp; stiril-laktona&nbsp; (+)-goniofufurona&nbsp; i&nbsp; 7-epi-(+)-goniofufurona&nbsp; polazeći&nbsp; iz&nbsp; D-glukoze.<br />Ispitana&nbsp; je&nbsp; in&nbsp; vitro&nbsp; citotoksičnost&nbsp; sintetizovanih&nbsp; analoga&nbsp; prema&nbsp; devet<br />malignih&nbsp; i&nbsp; jednoj&nbsp; zdravoj&nbsp; ćelijskoj&nbsp; liniji.&nbsp; Uspostavljeni&nbsp; su&nbsp; korelacioni&nbsp; odnosi<br />izmedju&nbsp; strukture&nbsp; i&nbsp; antiproliferati vne&nbsp; aktivnosti&nbsp; sintetizovanih&nbsp; proizvoda, pored&nbsp; toga&nbsp; uradjeni&nbsp; su&nbsp; i&nbsp; dodatni&nbsp; biolo&scaron;ki&nbsp; testovi&nbsp; koji&nbsp; se&nbsp; odnose&nbsp; na dokazivanje&nbsp; mehanizma&nbsp; citotoksičnog&nbsp; dejstva&nbsp; pomenutih&nbsp; stiril-laktona&nbsp; i analoga.</p> / <p>Multistep&nbsp; synthesis&nbsp; of&nbsp;&nbsp; a&nbsp; number&nbsp; of&nbsp; natural&nbsp; styryl&nbsp; lactones&nbsp;goniofufurone&nbsp; and&nbsp; 7-epi-goniofufurone&nbsp; analogues&nbsp; was&nbsp; achieved&nbsp;starting&nbsp; f rom&nbsp; D-glucose.&nbsp; In&nbsp; vitro&nbsp; cytotoxicity&nbsp; of&nbsp; newly&nbsp; synthetized analogues&nbsp; against&nbsp; nine&nbsp; human&nbsp; tumour&nbsp; cell&nbsp; lines&nbsp; and&nbsp; against&nbsp; a single normal cell line was evaluated. Structure-activity relationships were&nbsp; established&nbsp; for&nbsp; both&nbsp; natural&nbsp; products&nbsp; and&nbsp; analogues.&nbsp; Some additional&nbsp; biological&nbsp; tests&nbsp; related&nbsp; to&nbsp; the&nbsp; cell mechanisms&nbsp; underlying the&nbsp; cytotoxicity&nbsp; of&nbsp;&nbsp; the&nbsp; mentioned&nbsp; styryl&nbsp; lactones&nbsp; and&nbsp; analogues, were also carried out.</p>

À l’horizon 2024, l’expérience ATLAS prévoit de fonctionner à des luminosités 10 fois supérieures à la configuration actuelle. Par conséquent, l’électronique actuelle de lecture ne correspondra pas aux conditions de ces luminosités. Dans ces conditions, une nouvelle électronique devra être conçue. Cette mise à niveau est rendue nécessaire aussi par les dommages causés par les radiations et le vieillissement. Une nouvelle carte frontale va être intégrée dans l’électronique de lecture du calorimètre LAr. Un élément essentiel de cette carte est le Convertisseur Analogique-Numérique (CAN) présentant une résolution de 12bits pour une fréquence d’échantillonnage de 40MS/s, ainsi qu’une résistance aux irradiations. Compte tenu du grand nombre des voies, ce CAN doit remplir des critères sévères sur la consommation et la surface. Le but de cette thèse est de concevoir un CAN innovant qui peut répondre à ces spécifications. Une architecture à approximations successives (SAR) a été choisie pour concevoir notre CAN. Cette architecture bénéficie d’une basse consommation de puissance et d’une grande compatibilité avec les nouvelles technologies CMOS. Cependant, le SAR souffre de certaines limitations liées principalement aux erreurs de décisions et aux erreurs d’appariement des capacités du CNA. Deux prototypes de CAN-SAR 12bits ont été modélisés en Matlab afin d’évaluer leur robustesse. Ensuite les conceptions ont été réalisées dans une technologie CMOS 130nm d’IBM validée par la collaboration ATLAS pour sa tenue aux irradiations. Les deux prototypes intègrent un algorithme d’approximations avec redondance en 14 étapes de conversion, qui permet de tolérer des marges d’erreurs de décisions et d’ajouter une calibration numérique des effets des erreurs d’appariement des capacités. La partie logique de nos CAN est très simplifiée pour minimiser les retards de génération des commandes et la consommation d’énergie. Cette logique exécute un algorithme monotone de commutation des capacités du CNA permettant une économie de 70% de la consommation dynamique par rapport à un algorithme de commutation classique. Grâce à cet algorithme, une réduction de capacité totale est aussi obtenue : 50% en comparant notre premier prototype à un seul segment avec une architecture classique. Pour accentuer encore plus le gain en termes de surface et de consommation, un second prototype a été réalisé en introduisant un CNA à deux segments. Cela a abouti à un gain supplémentaire d’un facteur 7,64 sur la surface occupée, un facteur de 12 en termes de capacité totale, et un facteur de 1,58 en termes de consommation. Les deux CAN consomment respectivement une puissance de ~10,3mW et ~6,5mW, et ils occupent respectivement une surface de ~2,63mm2 et ~0,344mm2.Afin d’améliorer leurs performances, un algorithme de correction numérique des erreurs d’appariement des capacités a été utilisé. Des buffers de tensions de référence ont étés conçus spécialement pour permettre la charge/décharge des capacités du convertisseur en hautes fréquences et avec une grande précision. En simulations électriques, les deux prototypes atteignent un ENOB supérieur à 11bits tout en fonctionnant à la vitesse de 40MS/s. Leurs erreurs d’INL simulés sont respectivement +1,14/-1,1LSB et +1,66/-1,72LSB.Les résultats de tests préliminaires du premier prototype présentent des performances similaires à celles d’un CAN commercial de référence sur notre carte de tests. Après la correction, ce prototype atteint un ENOB de 10,5bits et un INL de +1/-2,18LSB. Cependant suite à une panne de carte de tests, les résultats de mesures du deuxième prototype sont moins précis. Dans ces circonstances, ce dernier atteint un ENOB de 9,77bits et un INL de +7,61/-1,26LSB. En outre la carte de tests actuelle limite la vitesse de fonctionnement à ~9MS/s. Pour cela une autre carte améliorée a été conçue afin d’atteindre un meilleur ENOB, et la vitesse souhaitée. Les nouvelles mesures vont être publiées dans le futur. / By 2024, the ATLAS experiment plan to operate at luminosities 10 times the current configuration. Therefore, many readout electronics must be upgraded. This upgrade is rendered necessary also by the damage caused by years of total radiations’ effect and devices aging. A new Front-End Board (FEB) will be designed for the LAr calorimeter readout electronics. A key device of this board is a radiation hard Analog-to-Digital Converter (ADC) featuring a resolution of 12bits at 40MS/s sampling rate. Following the large number of readout channels, this ADC device must display low power consumption and also a low area to easy a multichannel design.The goal of this thesis is to design an innovative ADC that can deal with these specifications. A Successive Approximation architecture (SAR) has been selected to design our ADC. This architecture has a low power consumption and many recent works has shown his high compatibility with modern CMOS scaling technologies. However, the SAR has some limitations related to decision errors and mismatches in capacitors array.Using Matlab software, we have created the models for two prototypes of 12bits SAR-ADC which are then used to study carefully their limitations, to evaluate their robustness and how it could be improved in digital domain.Then the designs were made in an IBM 130nm CMOS technology that was validated by the ATLAS collaboration for its radiation hardness. The prototypes use a redundant search algorithm with 14 conversion steps allowing some margins with comparator’s decision errors and opening the way to a digital calibration to compensate the capacitors mismatching effects. The digital part of our ADCs is very simplified to reduce the commands generation delays and saving some dynamic power consumption. This logic follows a monotonic switching algorithm which saves about70% of dynamic power consumption compared to the conventional switching algorithm. Using this algorithm, 50% of the total capacitance reduction is achieved when one compare our first prototype using a one segment capacitive DAC with a classic SAR architecture. To boost even more our results in terms of area and consumption, a second prototype was made by introducing a two segments DAC array. This resulted in many additional benefits: Compared to the first prototype, the area used is reduced in a ratio of 7,6, the total equivalent capacitance is divided by a factor 12, and finally the power consumption in improved by a factor 1,58. The ADCs respectively consume a power of ~10,3mW and ~6,5mW, and they respectively occupy an area of ~2,63mm2 and ~0,344mm2.A foreground digital calibration algorithm has been used to compensate the capacitors mismatching effects. A high frequency open loop reference voltages buffers have been designed to allow the high speed and high accuracy charge/discharge of the DAC capacitors array.Following electrical simulations, both prototypes reach an ENOB better than 11bits while operating at the speed of 40MS/s. The INL from the simulations were respectively +1.14/-1.1LSB and +1.66/-1.72LSB.The preliminary testing results of the first prototype are very close to that of a commercial 12bits ADC on our testing board. After calibration, we measured an ENOB of 10,5bits and an INL of +1/-2,18LSB. However, due to a testing board failure, the testing results of the second prototype are less accurate. In these circumstances, the latter reached an ENOB of 9,77bits and an INL of +7,61/-1,26LSB. Furthermore the current testing board limits the operating speed to ~9MS/s. Another improved board was designed to achieve a better ENOB at the targeted 40MS/s speed. The new testing results will be published in the future.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A cobertura regular de quase todo o planeta por sistemas de radar de abertura sintÃtica (synthetic aperture radar - SAR) orbitais e o uso de sistemas aerotransportados tÃm propiciado novos meios para obter informaÃÃes atravÃs do sensoriamento remoto de vÃrias regiÃes de nosso planeta, muitas delas inacessÃveis. Este trabalho trata do processamento de imagens digitais geradas por radar de abertura sintÃtica, especificamente da segmentaÃÃo, que consiste do isolamento ou particionamento dos objetos relevantes presentes em uma cena. A segmentaÃÃo de imagens digitais visa melhorar a interpretaÃÃo das mesmas em procedimentos subseqÃentes. As imagens SAR sÃo corrompidas por ruÃdo coerente, conhecido por speckle, que mascara pequenos detalhes e zonas de transiÃÃo entre os objetos. Tal ruÃdo à inerente ao processo de formaÃÃo dessas imagens e dificulta tarefas como a segmentaÃÃo automÃtica dos objetos existentes e a identificaÃÃo de seus contornos. Uma possibilidade para efetivar a segmentaÃÃo de imagens SAR consiste na filtragem preliminar do ruÃdo speckle, como etapa de tratamento dos dados. A outra possibilidade, aplicada neste trabalho, consiste em segmentar diretamente a imagem ruidosa, usando seus pixels originais como fonte de informaÃÃo. Para isso, à desenvolvida uma metodologia de segmentaÃÃo baseada em crescimento e fusÃo estatÃstica de regiÃes, que requer alguns parÃmetros para controlar o processo. As vantagens da utilizaÃÃo dos dados originais para realizar a segmentaÃÃo de imagens de radar sÃo a eliminaÃÃo de etapas de prÃ-processamento e o favorecimento da detecÃÃo das estruturas presentes nas mesmas. à realizada uma avaliaÃÃo qualitativa e quantitativa das imagens segmentadas, sob diferentes situaÃÃes, aplicando a tÃcnica proposta em imagens de teste contaminadas artificialmente com ruÃdo multiplicativo. Este segmentador à aplicado tambÃm no processamento de imagens SAR reais e os resultados sÃo promissores. / The regular coverage of the planet surface by spaceborne synthetic aperture radar (SAR)and also airborne systems have provided alternative means to gather remote sensing information of various regions of the planet, even of inaccessible areas. This work deals with the digital processing of synthetic aperture radar imagery, where segmentation is the main subject. It consists of isolating or partitioning relevant objects in a scene, aiming at improving image interpretation and understanding in subsequent tasks. SAR images are contaminated by coherent noise, known as speckle, which masks small details and transition zones among the objects. Such a noise is inherent in radar image generation process, making difficult tasks like automatic segmentation of the objects, as well as their contour identification. To segment radar images, one possible way is to apply speckle filtering before segmentation. Another one, applied in this work, is to perform noisy image segmentation using the original SAR pixels as input data, without any preprocessing,such as filtering. To provide segmentation, an algorithm based on region growing and statistical region merging has been developed, which requires some parameters to control the process. This task presents some advantages, as long as it eliminates preprocessing steps and favors the detection of the image structures, since original pixel information is exploited. A qualitative and quantitative performance evaluation of the segmented images is also executed, under different situations, by applying the proposed technique to simulated images corrupted with multiplicative noise. This segmentation method is also applied to real SAR images and the produced results are promising.